A Badros

A Gratwohl

AA Chanan-Khan

AJ Ashcroft

AP Ng

B Barlogie

B Bruno

BB Bjorkstrand

CS Mitsiades

D Chauhan

D Gupta

DE Speed

FE Davies

G Gahrton

H Brenner

ICM MacLennan

J Blade

JA Child

JM Mitchell

JP Fermand

K Dredge

KC Kose

KJ Phekoo

KS Peggs

LG Corral

M Attal

MA Dimopoulos

PG Richardson

S Schey

SA Schey

SV Rajkumar

SY Kristinsson

English

PubMed

B Rachet

E Mitry

A Shah

N Cooper

M P Coleman

F Berrino

A Blair

MP Coleman

E Lynge

MJ Quinn

P Richardson

JM Stellman

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Survival from multiple myeloma in England and Wales up to 2001

Rachet, B

Mitry, E

Shah, A

Cooper, N

Coleman, MP

LSHTM Research Online

Rachet, B; Mitry, E; Shah, A; Cooper, N; Coleman, MP (2008)Survival from multiple myeloma in England and Wales up to 2001.British journal of cancer, 99 Suppl 1. S110-2. ISSN 0007-0920Downloaded from: http://researchonline.lshtm.ac.uk/6966/Usage GuidelinesPlease refer to usage guidelines at http://researchonline.lshtm.ac.uk/policies.html or alterna-tively contact researchonline@lshtm.ac.uk.Available under license: Creative Commons Attribution Non-commercial No Derivativeshttp://creativecommons.org/licenses/by-nc-nd/2.5/Survival AnalysisSurvival from multiple myeloma in England and Wales up to 2001B Rachet1, E Mitry2, A Shah1, N Cooper3 and MP Coleman*,11Cancer Research UK Cancer Survival Group, Non-Communicable Disease Epidemiology Unit, Department of Epidemiology and Population Health,London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK ; 2De´partement d’He´patogastroente´rologie et OncologieDigestive, Centre Hospitalo-Universitaire Ambroise-Pare´, 9 avenue Charles de Gaulle, Boulogne F-92100, France; 3Social and Health Analysis andReporting Division, Off ice for National Statistics (Room FG/114), 1 Myddelton Street, London EC1R 1UW, UKBritish Journal of Cancer (2008) 99, S110 – S112. doi:10.1038/sj.bjc.6604607 www.bjcancer.comPublished online 23 September 2008& 2008 Cancer Research UKMultiple myeloma is an uncommon neoplasm of plasma cellsaffecting mainly the elderly; it is rare under the age of 50 years.Each year in England and Wales, approximately 1800 cases areregistered in men (1.5% of all malignancies) and 1500 in women(1.2% of all malignancies). Incidence has increased steadily sincethe 1980s in both sexes in many countries, including England andWales (Coleman et al, 1993; Quinn et al, 2001). Incidence is slightlyhigher in men, and it has risen by approximately 12% in both sexessince the mid-1980s to reach 6.1 per 100 000 per year in men and5.5 in women by 1999. No marked socioeconomic gradient inincidence has previously been reported in England and Wales, butthe most deprived fifth of the population provides a strikingexception to the overall trend in the 1990s: incidence rates in thisgroup increased very little in either sex, and by 1999, annualincidence was 20–25% lower than in the other four deprivationgroups (4.5 and 4 per 100 000 in men and women, respectively).The aetiology of myeloma is unknown, although exposure toionising radiation is a cause (IARC, 2000) and occupationalexposure to chemicals, such as ethylene oxide, styrene and vinylchloride have been suggested as risk factors (Blair and Kazerouni,1997; Lynge et al, 1997; Stellman, 1998).Myeloma is characterised by a malignant clone of plasmacells invading bone marrow, with high serum or urine levelsof monoclonal immunoglobulin (usually a g-globulin), and lyticbone lesions. It is often preceded by a latent monoclonal gammo-pathy of uncertain or undetermined clinical significance, whichmay last for years before evolving into malignant myelomaproper. Monoclonal gammopathy of uncertain or undeterminedclinical significance may be diagnosed incidentally from routineexamination of serum or a blood film, and in the minorityof patients who do go on to develop myeloma, the date of diagnosis– and thus the recorded duration of survival – will depend on thefrequency and diagnostic intensity of clinical follow-up (Berrinoet al, 1995). Part of the increase in incidence may be attributable tothe improved sensitivity of diagnostic tests, but environmentalexposure to toxins may also underlie a real increase (Richardsonet al, 2004).Myeloma comprised 96% of the malignant monoclonal gammo-pathies throughout the period 1986–1999, whereas plasmacytomaaccounted for most of the remainder.Almost 40 000 adults were registered with multiple myelomain England and Wales during the 14-year period 1986–1999.Approximately 18% of patients otherwise eligible for survivalanalysis were excluded, mostly (13%) because their recordedduration of survival was zero (date of diagnosis same as the date ofdeath). Some of these patients will have been diagnosed on the dayof death, but in many cases the cancer registration was based solelyon the death certificate; hence, the date of diagnosis was unknown.It was not possible to distinguish these cases in the available dataand all patients with ‘zero survival’ were thus excluded. The vitalstatus of 1.6% of eligible patients was unknown on 5 November2002, when the data were extracted for analysis, and a further 3%were excluded because myeloma was not their first primarymalignancy. The distribution of patients in these categories wasfairly stable over the period 1986–1999 and similar in alldeprivation groups (data not shown); hence, the exclusions areunlikely to have had a large impact on time trends or thedeprivation gradient in survival.SURVIVAL TRENDSFor patients diagnosed during 1996–1999, relative survival wasapproximately 62% at 1 year and 25% at 5 years, whereas 10-yearsurvival was only 10–11% for patients diagnosed during the early1990s (Table 1). Survival is now 1–2% higher in men, but thedifferences are not significant. After adjustment for changes in thedistribution of patients by deprivation category, 5-year survival isseen to have risen significantly over the 14-year period 1986–1999,by an average of approximately 5% every 5 years (4.4% in men,5.8% in women). In fact, most of the increase occurred during the1990s (Figure 1). One-year survival also increased significantlyfor men (3.8% every 5 years) to 62.9% (Table 1, Figure 1), butthe small increase for women was not significant. There was nosignificant increase in 10-year survival between patients diagnosedin the late 1980s and those diagnosed in the early 1990s.Hybrid analysis (Brenner and Rachet, 2004) suggests that forpatients diagnosed during 2000–2001, the national average relativesurvival up to 5 years should remain stable (Table 1).DEPRIVATIONOne-year survival has been consistently and significantly higherfor more affluent men. The deprivation gap widened from 5*Correspondence: Professor MP Coleman;E-mail: michel.coleman@lshtm.ac.ukBritish Journal of Cancer (2008) 99, S110 – S112& 2008 Cancer Research UK All rights reserved 0007 – 0920/08 $32.00www.bjcancer.comto 8% during the period 1986–1999 (Table 2), although theaverage change in the gap every 5 years (1.2%) was not itselfstatistically significant. For women, the deprivation gap in 1-yearsurvival is not significant.There was no significant difference in 5-year survivalamong deprivation categories for men diagnosed during1986– 1990. The deprivation gap of þ 3.4% in 5-year survivalamong women diagnosed at that time (higher survival inmore deprived women) is unusual, but it was of borderlinestatistical significance (Table 2), and the data are well fittedby a simple linear regression (Figure 2). Furthermore, the positivedeprivation gap in 10-year survival for women diagnosed duringthe late 1980s (þ 4.6%, higher survival in the most deprived) wasstatistically significant at the 1% level.During the 1990s, however, the more typical deprivationpattern in 5-year survival emerged between both sexes (negativegradient; lower survival in the more deprived groups).The deprivation gap of 5% that has arisen for men diagnosedTable 1 Trends in relative survival (%) by sex, time since diagnosis and calendar period of diagnosis: England and Wales, adults (15–99 years) diagnosedduring 1986–1999 and followed up to 2001Calendar period of diagnosisaAverage change (%) Predictionc for patients1986–1990 1991–1995 1996–1999 every 5 yearsb diagnosed during 2000–2001Time sincediagnosisSurvival(%) 95% CISurvival(%) 95% CISurvival(%) 95% CISurvival(%) 95% CISurvival(%) 95% CI1 year Men 57.5 (56.1, 58.9) 60.6 (59.3, 61.9) 62.9 (61.5, 64.3) 3.8** (1.2, 6.5) 62.7 (60.8, 64.7)Women 57.3 (55.8, 58.7) 58.5 (57.2, 59.9) 60.9 (59.4, 62.4) 0.7 (2.1, 3.5) 60.5 (58.4, 62.6)5 years Men 20.8 (19.6, 22.1) 21.6 (20.5, 22.8) 25.6 (23.8, 27.4) 4.4** (1.6, 7.3) 25.8 (23.9, 27.8)Women 20.6 (19.4, 21.9) 20.4 (19.3, 21.6) 23.8 (22.0, 25.6) 5.8** (3.0, 8.7) 24.3 (22.3, 26.3)10 years Men 9.9 (8.9, 11.0) 10.7 (9.5, 12.0) 0.7 (3.5, 4.9) 14.6 (12.8, 16.6)Women 9.6 (8.6, 10.6) 9.5 (8.3, 10.7) 3.5 (0.4, 7.3) 11.7 (10.0, 13.6)CI¼ confidence interval. aSurvival estimated with cohort or complete approach (see Rachet et al, 2008). bMean absolute change (%) in survival every 5 years, adjusted fordeprivation (see Rachet et al, 2008). cSurvival estimated with hybrid approach (see Rachet et al, 2008). **Po0.01.020406080100Relative survival (%)0 2 4 6 8 10Years since diagnosisMen020406080100Relative survival (%)0 2 4 6 8 10Years since diagnosis2000– 20011996–19991991–19951986–1990WomenFigure 1 Relative survival (%) up to 10 years after diagnosis by sex andcalendar period of diagnosis: England and Wales, adults (15–99 years) diagnosedduring 1986–1999 and followed up to 2001. Survival estimated with cohort orcomplete approach (1986–1990, 1991–1995, 1996–1999) or hybridapproach (2000–2001) (see Rachet et al, 2008).0102030405-year relative survival (%)Affluent 2 3 4 DeprivedDeprivation categoryMen0102030405-year relative survival (%)Affluent 2 3 4 DeprivedDeprivation category2000 – 20011996 –19991991 –19951986 –1990WomenFigure 2 Trends in the deprivation gap in 5-year relative survival(%) by sex and calendar period of diagnosis: England and Wales,adults (15–99 years) diagnosed during 1986–1999 and followed upto 2001.Survival from multiple myeloma in England and WalesB Rachet et alS111British Journal of Cancer (2008) 99(S1), S110 – S112& 2008 Cancer Research UKin the late 1990s is of borderline significance. For women, thepositive deprivation gradient in myeloma survival (þ 3%,higher survival in more deprived women) in the late 1980shad completely reversed by the late 1990s: by then, the deprivationgap between the most deprived and the most affluent women(almost 8%, lower in more deprived women) had becomestatistically significant at 5%. The rate at which the deprivationgap in 5-year survival for women has widened (5.6% every 5 years)is itself significant (Table 2). Figure 2 illustrates these widedifferences among deprivation groups in survival trends, with noimprovement at all in 5-year survival among the most deprivedgroup, but an increase of more than 10% for the most affluentgroup, in which survival has now overtaken that in the most deprivedgroup.Short-term predictions with hybrid analysis suggest that thewide socioeconomic differences in survival are not likely to reducein the near future (Table 2).COMMENTDespite substantial overall gains in survival from multiplemyeloma, both short-term and long-term survival remains poor.Even for patients diagnosed 2000–2001, survival is predicted to bebelow 30% at 5 years, and below 15% at 10 years after diagnosis.The improvement has been small or negligible among the mostdeprived groups. As a result, the deprivation gaps in relativesurvival widened during the 1990s, even after changes inbackground mortality were adjusted for separately, within eachdeprivation group.One-year survival began increasing in the late 1980s, as did thecorresponding deprivation gap. A similar pattern is seen for 5-yearsurvival only from the mid-1990s. Long-term survival had notchanged until recently, but it is predicted to rise for patientsdiagnosed during 2000–2001. This pattern may reflect theincreasing influence of autologous bone marrow graft and stemcell transplantion, important therapeutic advances introducedfrom the late 1980s and early 1990s (Richardson et al, 2004). Theuse of drugs such as thalidomide is too recent to have had anyeffect on survival figures in this study.In 1986–1990, both incidence and survival were similar in alldeprivation groups. The more marked increase in both incidenceand survival among the more affluent groups may suggest thatthese groups have taken more advantage of earlier diagnosis. Earlydiagnosis has considerable prognostic significance, as autograft ismore successful if done at an early stage.REFERENCESBerrino F, Este`ve J, Coleman MP (1995) Basic issues in the estimationand comparison of cancer patient survival. In Survival of CancerPatients in Europe: the EUROCARE Study. (IARC Scientific PublicationsNo. 132), Berrino F, Sant M, Verdecchia A, Capocaccia R, Hakulinen T,Este`ve J (eds), pp 1 – 14. International Agency for Research on Cancer:LyonBlair A, Kazerouni N (1997) Reactive chemicals and cancer. Cancer CausesControl 8: 473 – 490Brenner H, Rachet B (2004) Hybrid analysis for up-to-date long-termsurvival rates in cancer registries with delayed recording of incidentcases. Eur J Cancer 40: 2494 – 2501Coleman MP, Este`ve J, Damiecki P, Arslan A, Renard H (1993) Trends inCancer Incidence and Mortality (IARC Scientific Publications No. 121).International Agency for Research on Cancer: LyonIARC (2000) IARC Monographs on the Evaluation of CarcinogenicRisks to Humans. Volume 75. Ionizing Radiation, Part I: X- andGamma (y) Radiation and Neutrons. International Agency for Researchon Cancer: LyonLynge E, Anttila A, Hemminki K (1997) Organic solvents and cancer.Cancer Causes Control 8: 406 – 419Quinn MJ, Babb P, Brock A, Kirby L, Jones J (2001) Cancer Trends inEngland and Wales 1950 – 1999. Studies on Medical and PopulationSubjects No. 66. Office for National Statistics: LondonRachet B, Woods LM, Mitry E, Riga M, Cooper N, Quinn MJ, Steward J, BrennerH, Este`ve J, Sullivan R, Coleman MP (2008) Cancer survival in England andWales at the end of the 20th century. Br J Cancer 99(Suppl 1): S2 – S10Richardson P, Hideshima T, Anderson KC (2004) Multiple myelomaand related disorders. In Clinical Oncology. Abeloff MD, ArmitageJO, Niederhuber JE, Kastan MB, McKenna WG (eds) (3rd edn),pp 2955 – 2984. Elsevier: PhiladephiaStellman JM (1998) Encyclopaedia of Occupational Health and Safety.4th edn. International Labour Office: GenevaTable 2 Trends in the deprivation gap in relative survival (%) by sex, time since diagnosis and calendar period of diagnosis: England and Wales, adults(15–99 years) diagnosed during 1986–1999 and followed up to 2001Calendar period of diagnosisaAverage change (%) Predictionc for patients1986–1990 1991–1995 1996–1999 every 5 yearsb diagnosed during 2000–2001Time sincediagnosisDeprivationgap (%) 95% CIDeprivationgap (%) 95% CIDeprivationgap (%) 95% CIDeprivationgap (%) 95% CIDeprivationgap (%) 95% CI1 year Men 5.3* (9.3, 1.2) 5.1** (8.8, 1.3) 7.6** (11.5, 3.6) 1.2 (4.2, 1.8) 7.1* (12.7, 1.5)Women 2.4 (6.6, 1.8) 2.4 (6.3, 1.5) 0.4 (3.9, 4.7) 1.4 (1.7, 4.6) 0.2 (5.9, 6.4)5 years Men 0.4 (3.2, 4.1) 3.1 (6.6, 0.4) 4.8 (10.0, 0.4) 2.8 (6.1, 0.4) 6.7* (12.3, 1.1)Women 3.4 (0.3, 7.0) 1.6 (5.1, 1.8) 7.7** (12.9, 2.6) 5.6** (8.8, 2.4) 5.8 (11.7, 0.1)10 years Men 1.2 (1.8, 4.2) 1.3 (2.3, 4.9) 0.1 (4.6, 4.8) 4.1 (9.5, 1.3)Women 4.6** (1.9, 7.4) 0.4 (3.1, 3.9) 4.3 (8.7, 0.2) 2.7 (7.7, 2.3)CI¼ confidence interval. aSurvival estimated with cohort or complete approach (see Rachet et al, 2008). bMean absolute change (%) in the deprivation gap in survival every5 years, adjusted for the underlying trend in survival (see Rachet et al, 2008). cSurvival estimated with hybrid approach (see Rachet et al, 2008). *Po0.05; **Po0.01.Survival from multiple myeloma in England and WalesB Rachet et alS112British Journal of Cancer (2008) 99(S1), S110 – S112 & 2008 Cancer Research UK

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Survival from multiple myeloma in England and Wales up to 2001

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